The invention generally relates to pharmaceutical compositions, such as drug formulations present in a solid form for oral administration. More particularly, the invention relates to long-lasting sustained dosage compositions, and carriers and active ingredients in the compositions thereof, such as extended release drug compositions for oral controlled release dosage formulations containing a drug and a carrier material.
Drug delivery at a predetermined rate such that drug concentrations can be maintained at therapeutically effective levels over an extended period, has received a great deal of attention. Many known solid drug formulations are required to be taken orally three times a day. There is a need for oral formulations to be taken less often, such as once per day.
Various approaches exist for preparing sustained or controlled release pharmaceutical formulations, such as various extended release formulations in tablet or capsule form. For example, one method of forming delayed or sustained release formulations includes coating the tablet with a release-retarding coating, or coating individual granules with such a coating, and compressing these coated granules into a tablet. One exemplary technique involves controlled release solid preparations for erythromycin derivatives in an alginate matrix, such as a matrix having a water-soluble alginate and a complex salt of alginic acid as described in U.S. Pat. No. 4,842,866, issued Jun. 27, 1989.
Another example involves controlled release tablet formulation for clarithromycin by using a matrix or carrier at high concentration of 5% to 50% of hydroxypropyl methylcellulose, such as 10%, 20% or 30% of hydroxypropyl methylcellulose, to be mixed or dispersed throughout the tablet, as described in U.S. Pat. No. 6,010,718, issued on Jan. 4, 2000.
However, in the preparation of delayed or sustained release forms of drug active ingredients, high concentration of soluble polymers often result in extremely slow drug dissolution, poor or variable drug release, poor or variable absorption, and acid instability at variable pH environments throughout the whole gastrointestinal (GI) tract. This is especially significant for relatively insoluble drug active ingredients, such as some poorly soluble antibiotics, e.g., macrolide antibiotics, which have been used extensively in treating a wide range of bacterial infections. Particularly, such problems occur when formulating erythromycin and its derivatives, such as 6-O-methylerythromycin A (clarithromycin), useful in treating common infections of the middle ear and upper respiratory tract.
Therefore, there is a need for an improved controlled release formulation and method for preparing such a controlled release formulation, and for a method of treating infection.